The importance of myocardial ion-exchange in controlling excitation-contraction coupling and myocardial function is generally accepted, however, primarily due to the lack of an appropriate preparation for studying ion-exchange kinetics, information on sequential alterations in ion-exchange during pathological oxygen deprivation is not available. The objectives of this proposed three year investigation will be to define the anoxic-induced alterations in myocardial ion-exchange kinetics, to develop information toward understanding the basic mechanisms responsible for these alterations and, to relate these to the changes in mechanical performance, electrical and metabolic parameters observed during oxygen deprivation. The proposed research will employ three basic preparations: The isolated, arterially perfused interventricular septa of white rabbits, isolated rabbit papillary muscles, and cultured heart cells of rats. Established on-line labeling and washout techniques will be utilized to investigate the sequential exchange kinetics of 42K, 24Na, 36C1, 85Sr, 133Ba, 51Cr-EDTA and 45Ca. A "flexible" microelectrode technique will be utilized to monitor intracellular electrical activity. Mechanical performance parameters will be measured with standard force transducer method and by crossbridge activation analysis. This research should provide the first information on sequential ion fluxes during oxygen deprivation and will allow evaluation of the relationships between sarcolemmal ion-exchange, electrical activity, E-C coupling and the decline of myocardial mechanical function observed during anoxemia.